Abstract
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Objectives Molecular imaging techniques allow for in vivo imaging of, e.g., receptors and transporters in the human brain and they are used to measure drug-induced changes in endogenous neurotransmitters. Pharmacological magnetic resonance imaging (phMRI), on the other hand, offers the potential to localize the drug associated neurovascular changes in the brain. By simultaneously acquiring MR- and PET-data under a pharmacological challenge important information about how the pharmacologically induced vascular effects are induced by the regional neurochemical changes can be achieved.
Methods An anesthetized rhesus macaque underwent simultaneous PET- and MR-scannings with a 3T Tim Trio with a BrainPET insert inside the bore of the scanner; data were acquired continously for 140 min. Prior to scanning, iron oxide was injected to improve contrast and detection power of fMRI. The 5-HT1B receptor radioligand [11C]AZ10419369 was given in a bolus plus infusion schedule (Kbol=3). Regional time-activity curves were retrieved by co-registration to the anatomical MRI-image. Eighty min after bolus injection, the 5-HT releaser fenfluramine (5mg/kg) was infused i.v. over 5 min. fMRI images were analyzed according to a GLM model with a single drug challenge. Cerebral 5-HT1B receptor binding was quantified at steady-state levels to generate BPND with cerebellum as the reference region.
Results Time-activity curves of [11C]AZ10419369 showed that steady-state levels were achieved within the first 60 min. Fenfluramine infusion led to a ~30% reduction in occipital cortex BPND. The challenge was associated with an increase in cerebral blood volume in a regional pattern corresponding to the distribution of 5-HT rich fibres (putamen, caudate, midbrain).
Conclusions Simultaneous MR- and PET-data acquisition is a promising tool for investigating in vivo effects of the brain serotoneric neurotransmission